Pharmacogenetics and patient categories MCQs With Answer

Pharmacogenetics and patient categories MCQs With Answer (M.Pharm – Drug Delivery Systems, MPH 102T)

Pharmacogenetics bridges genetic variability with pharmacokinetics, pharmacodynamics and the design of drug delivery systems. For M.Pharm students, mastering how polymorphisms in enzymes, transporters and immune markers reshape dose, route, and formulation choices is vital for precision therapeutics. This quiz focuses on clinically relevant genotypes (CYPs, UGT1A1, SLCO1B1, ABCB1, HLA alleles, TPMT/NUDT15, NAT2, G6PD) and patient categories (pediatric, geriatric, pregnancy, organ impairment) that drive decisions such as bypassing first-pass metabolism, avoiding prodrugs, deploying TDM, or choosing safer formulations. The questions below challenge you to integrate pharmacogenetic evidence with delivery strategy—helping you translate genotype data into optimal dosing, selection of route, and risk mitigation in diverse populations.

Q1. Which statement best captures the role of pharmacogenetics in drug delivery design?

• Inherited variants alter drug-metabolizing enzymes and transporters, guiding dose, route, and formulation choices
• Adverse effects relate only to excipients and not to genes
• Environmental factors fully determine bioavailability, not genotype
• Device selection alone can overcome all interpatient variability

Correct Answer: Inherited variants alter drug-metabolizing enzymes and transporters, guiding dose, route, and formulation choices

Q2. A patient with CYP2D6 poor metabolizer status is given codeine. What is the most likely clinical outcome?

• Minimal analgesia due to insufficient conversion to morphine
• Exaggerated analgesia and toxicity due to rapid activation
• Normal analgesia at standard doses
• Life-threatening respiratory depression at standard doses

Correct Answer: Minimal analgesia due to insufficient conversion to morphine

Q3. In CYP2C19 loss-of-function carriers needing antiplatelet therapy after PCI, the preferred strategy is:

• Continue clopidogrel at standard dose
• Increase clopidogrel dose twofold
• Use a non–CYP2C19 dependent P2Y12 inhibitor (e.g., prasugrel or ticagrelor)
• Stop all antiplatelets and rely on aspirin alone

Correct Answer: Use a non–CYP2C19 dependent P2Y12 inhibitor (e.g., prasugrel or ticagrelor)

Q4. Which genotype combination predicts the lowest warfarin maintenance dose?

• VKORC1 −1639 GG with CYP2C9 *1/*1
• VKORC1 −1639 AA with CYP2C9 *3/*3
• VKORC1 −1639 GA with CYP2C9 *1/*2
• VKORC1 −1639 GG with CYP2C9 *2/*2

Correct Answer: VKORC1 −1639 AA with CYP2C9 *3/*3

Q5. For a patient with TPMT or NUDT15 poor metabolizer status starting thiopurines (e.g., azathioprine/6-MP), the best initial approach is:

• Use standard dose and monitor liver enzymes only
• Start at markedly reduced dose (e.g., 5–10% of standard) or consider a non-thiopurine alternative
• Switch to extended-release thiopurine
• Add a CYP3A inhibitor to boost exposure

Correct Answer: Start at markedly reduced dose (e.g., 5–10% of standard) or consider a non-thiopurine alternative

Q6. UGT1A1*28 homozygosity is most strongly associated with which irinotecan-related risk and action?

• Reduced diarrhea; increase the dose
• Increased neutropenia; consider a lower starting dose or alternative regimen
• No change in toxicity; standard dosing is adequate
• Only infusion reactions; premedicate with steroids

Correct Answer: Increased neutropenia; consider a lower starting dose or alternative regimen

Q7. Patients with SLCO1B1 c.521T>C (decreased OATP1B1 function) on simvastatin have elevated myopathy risk. A CPIC-consistent strategy is:

• Increase simvastatin dose to overcome reduced hepatic uptake
• Switch to a statin with lower OATP1B1 dependence (e.g., pravastatin or fluvastatin) or use a lower simvastatin dose
• Add a CYP2C19 inducer
• Change to extended-release simvastatin to reduce Cmax

Correct Answer: Switch to a statin with lower OATP1B1 dependence (e.g., pravastatin or fluvastatin) or use a lower simvastatin dose

Q8. Before initiating carbamazepine in patients of Southeast Asian ancestry, the most critical genetic screen to prevent SJS/TEN is:

• HLA-B*57:01
• HLA-B*15:02
• HLA-A*31:01
• HLA-DRB1*07:01

Correct Answer: HLA-B*15:02

Q9. A patient tests positive for HLA-B*57:01. The safest action regarding abacavir is to:

• Proceed with abacavir and monitor closely
• Use abacavir only in modified-release form
• Avoid abacavir and choose an alternative NRTI
• Give abacavir with steroid premedication

Correct Answer: Avoid abacavir and choose an alternative NRTI

Q10. Increased intestinal P-glycoprotein (ABCB1) expression will most likely cause which outcome for an oral P-gp substrate, and what delivery approach can mitigate it?

• Higher bioavailability; use oral immediate-release
• Lower systemic exposure; consider parenteral or sublingual delivery to bypass gut efflux
• No change; P-gp acts only in the liver
• Lower exposure; use extended-release to overcome efflux

Correct Answer: Lower systemic exposure; consider parenteral or sublingual delivery to bypass gut efflux

Q11. The ABCG2 (BCRP) c.421C>A (Q141K) variant reduces transporter function. For rosuvastatin therapy, a reasonable action is:

• Increase the dose to achieve target LDL-C
• Initiate at a lower dose due to increased exposure
• Switch to simvastatin to avoid transporter effects
• Add a BCRP inducer

Correct Answer: Initiate at a lower dose due to increased exposure

Q12. NAT2 slow acetylators receiving isoniazid are at increased risk of toxicity. The preferred management is:

• No change; NAT2 status is clinically irrelevant
• Provide pyridoxine supplementation and consider dose reduction with therapeutic drug monitoring
• Add rifampicin to induce NAT2
• Use enteric-coated isoniazid to avoid toxicity

Correct Answer: Provide pyridoxine supplementation and consider dose reduction with therapeutic drug monitoring

Q13. In G6PD-deficient patients, which statement regarding oxidative drugs (e.g., primaquine, rasburicase) is most accurate for delivery planning?

• Safe at standard doses if given intravenously
• Risk of hemolysis mandates avoidance or use of safer alternatives with close monitoring
• Only extended-release formulations cause hemolysis
• Topical delivery eliminates systemic risk

Correct Answer: Risk of hemolysis mandates avoidance or use of safer alternatives with close monitoring

Q14. For a high–first-pass prodrug mainly activated by hepatic CYP3A, which route most effectively minimizes genotype-driven variability in activation?

• Oral extended-release
• Intravenous administration
• Enteric-coated oral capsules
• Rectal suppositories

Correct Answer: Intravenous administration

Q15. Which statement best reflects the interplay of ontogeny and genotype when designing therapies for neonates and infants?

• Genotype always overrides developmental stage
• Developmental immaturity of enzymes/transporters can overshadow genotype, necessitating age-appropriate dosing and formulations
• Formulation changes remove the need for age-based dosing
• Only transporter genes matter in pediatrics

Correct Answer: Developmental immaturity of enzymes/transporters can overshadow genotype, necessitating age-appropriate dosing and formulations

Q16. Reduced SLCO1B1 function can delay methotrexate clearance. An appropriate action in high-dose MTX therapy is:

• Eliminate leucovorin rescue
• Use intensified leucovorin rescue and vigilant pharmacokinetic monitoring
• Switch to oral MTX to avoid toxicity
• Add a P-gp inhibitor

Correct Answer: Use intensified leucovorin rescue and vigilant pharmacokinetic monitoring

Q17. CYP3A5 expressers (e.g., CYP3A5*1 carriers) on tacrolimus typically require:

• Lower starting doses due to slow clearance
• Higher starting doses due to faster clearance
• No dose adjustment; TDM is unnecessary
• Switch to cyclosporine

Correct Answer: Higher starting doses due to faster clearance

Q18. For NSCLC patients with activating EGFR mutations, the pharmacogenetically aligned strategy is to:

• Use nonselective cytotoxics only
• Initiate an EGFR tyrosine kinase inhibitor (e.g., gefitinib, erlotinib, osimertinib)
• Use anti-VEGF therapy regardless of genotype
• Prefer intramuscular delivery of any chemotherapy

Correct Answer: Initiate an EGFR tyrosine kinase inhibitor (e.g., gefitinib, erlotinib, osimertinib)

Q19. In geriatrics with polypharmacy, comorbid renal impairment, and multiple actionable genotypes, the most rational precision strategy is:

• Single-gene testing only when adverse events occur
• Pre-emptive multigene panel testing integrated with therapeutic drug monitoring and deprescribing
• Avoid monitoring to reduce complexity
• Use controlled-release formulations to negate genetic variability

Correct Answer: Pre-emptive multigene panel testing integrated with therapeutic drug monitoring and deprescribing

Q20. Which statement about CPIC in clinical pharmacogenetics is correct for implementation in drug delivery decisions?

• CPIC develops clinical trials but not dosing guidelines
• CPIC provides peer-reviewed, gene–drug dosing recommendations that can be embedded in e-prescribing systems
• CPIC focuses only on oncology drugs
• CPIC replaces clinical judgment and TDM

Correct Answer: CPIC provides peer-reviewed, gene–drug dosing recommendations that can be embedded in e-prescribing systems

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